The purpose of these studies is to identify, characterize and isolate endogenous genes of mice that correlate with the Mendelian segregation of susceptibility to mammary cancer. During this past year, we have shown that the segregation of mammary tumorigenesis in crosses of GR mice resembles that observed in certain high risk breast cancer families, i.e., (C57BL x (C57BL x GR)Fl) backcross (BCl) mice have a 50% incidence in breast cancer. We have defined the mammary tumor virus (MMTV) genetic information in C57BL, GR, Fl, and BCl mice by both liquid hybridization and restriction endonuclease analyses. This has led to the identification of those endogenous genetic elements of GR mice that give a 100% correlation with the segregation of susceptibility to mammary tumorigenesis. Restriction endonuclease analysis of DNA from blood samples of intact young adult female mice have revealed which siblings of a given litter will eventually develop mammary cancer within one year. This system, therefore, has also provided an excellent in-vivo model to distinguish among tumor initiations, cocarcinogens, and tumor promotion.